This invention relates to the chemoprevention of prostate cancer and, more particularly, to a method of suppressing or inhibiting latent prostate cancer comprising administering to a mammalian subject a chemopreventive agent and analogs and metabolites thereof. The chemopreventive agent prevents, prevents recurrence of, suppresses or inhibit prostate carcinogenesis; and treats prostate cancer.
Prostate cancer is one of the most frequently occurring cancers among men in the United States, with hundreds of thousands of new cases diagnosed each year. Unfortunately, over sixty percent of newly diagnosed cases of prostate cancer are found to be pathologically advanced, with no cure and a dismal prognosis. One approach to this problem is to find prostate cancer earlier through screening programs and thereby reduce the number of advanced prostate cancer patients. Another strategy, however, is to develop drugs to prevent prostate cancer. One third of all men over 50 years of age have a latent form of prostate cancer that may be activated into the life-threatening clinical prostate cancer form. The frequency of latent prostate tumors has been shown to increase substantially with each decade of life from the 50s (5.3-14%) to the 90s (40-80%). The number of people with latent prostate cancer is the same across all cultures, ethnic groups, and races, yet the frequency of clinically aggressive cancer is markedly different. This suggests that environmental factors may play a role in activating latent prostate cancer. Thus, the development of chemoprevention strategies against prostate cancer may have the greatest overall impact both medically and economically against prostate cancer.
Toremifene is an example of a triphenylalkene compound described in U.S. Pat. Nos. 4,696,949 and 5,491,173 to Toivola et al., the disclosures of which are incorporated herein by reference. The parenteral and topical administration to mammalian subjects of formulations containing toremifene are described in U.S. Pat. No. 5,571,534 to Jalonen et al. and in U.S. Pat. No. 5,605,700 to DeGregorio et al., the disclosures of which are incorporated herein by reference.
U.S. Pat. No. 5,595,985 to Labrie, the disclosure of which is incorporated herein by reference, also describe a method for treating benign prostatic hyperplasia using a combination of a 5xcex1-reductase inhibitor and a compound that binds and blocks access to androgen receptors. One example of a compound that blocks androgen receptors is flutamide.
U.S. Pat. Nos. 4,329,364 and 4,474,813 to Neri et al., the disclosures of which are incorporated herein by reference, describe pharmaceutical preparations comprising flutamide for delaying and/or preventing the onset of prostate carcinoma. The preparation can be in the form of a capsule, tablet, suppository, or elixir. Despite these developments, there is a continuing need for agents and methods effective for preventing prostate cancer.
Because of the high incidence and mortality of prostate cancer, it is imperative to develop chemoprevention strategies against this devastating disease. Understanding those factors that contribute to prostate carcinogenesis including the initiation, promotion, and progression of prostate cancer will provide molecular mechanistic clues as to appropriate points of intervention to prevent or halt the carcinogenic process. New innovative approaches are urgently needed at both the basic science and clinical levels to decrease the incidence of prostate cancer as well as to halt or cause the regression of latent prostate cancer. As the frequency of prostate cancer escalates dramatically at the same ages when men are confronted by other competing causes of mortality, simply slowing the progression of prostate adenocarcinoma may be both a more suitable and cost effective health strategy. The present invention is directed to satisfying this need.
Further, as prostate intraepithelial neoplasia is in the direct causal pathway to prostate cancer and its presence specifically portends an increased risk of prostate cancer, men diagnosed with prostate intraepithelial neoplasia have dramatic changes in their quality of life. The only way to diagnose prostate intraepithelial neoplasia is by prostate biopsy. Once the diagnosis of prostate intraepithelial neoplasia is made, however, the standard of medical care is that the patient must be subjected to more frequent biopsies and physician visits. In addition, there is great patient and physician anxiety because the diagnosis of prostate cancer is imminent. Currently, there is no treatment available for patients who have prostate intraepithelial neoplasia.
This invention related to a method for preventing prostate carcinogenesis of a subject comprising: administering to a mammalian subject, a pharmaceutical preparation comprising an anti-estrogen, or its analog, derivative, isomer, and metabolite thereof; and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof.
This invention relates to method of suppressing or inhibiting latent prostate cancer of a subject comprising: administering to a mammalian subject, a pharmaceutical preparation comprising an anti-estrogen, or its analog, derivative, isomer, and metabolite thereof, and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof.
This invention relates to a method for reducing the risk of developing prostate cancer of a subject comprising: administering to a mammalian subject, a pharmaceutical preparation comprising an anti-estrogen, or its analog, derivative, isomer, and metabolite thereof, and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof.
This invention relates to a method for increasing the survival rate of a subject having prostate cancer comprising: administering to a mammalian subject, a pharmaceutical preparation comprising an anti-estrogen, or its analog, derivative, isomer, and metabolite thereof, and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof.
This invention relates to a method of treating a subject with prostate cancer comprising: administering to a mammalian subject, a pharmaceutical preparation comprising an anti-estrogen, or its analog, derivative, isomer, and metabolite thereof, and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof.
This invention related to a method for reducing the amount of precancerous precursors of prostate adenocarcinoma lesions of a subject comprising: administering to a mammalian subject, a pharmaceutical preparation comprising an anti-estrogen, or its analog, derivative, isomer, and metabolite thereof, and their pharmaceutically acceptable salts, esters, or N-oxides, and mixtures thereof.
In one embodiment the antiestrogen is a selective estogen receptor modulator (SERM), a triphenylethylene or a triphenyalkane. In one embodiment the precancerous precursor of prostate adenocarcinoma is prostate intraepithelial neoplasia (PIN). In one embodiment the precancerous precursor of prostate adenocarcinoma is high grade prostate intraepithelial neoplasia (PIN).
The present invention provides a safe and effective method for preventing prostate carcinogenesis, suppressing or inhibiting latent prostate cancer and is particularly useful for treating subjects having an elevated risk of developing prostate cancer, for example, those having benign prostatic hyperplasia, prostate intraepithelial neoplasia (PIN), or an abnormally high level of circulating prostate specific antibody (PSA), or who have a family history of prostate cancer.